Category Archives: Campus Life

Post navigation

Editor’s note: This article was originally published as Twenty-four visits to Stockholm: a concise history of the Rockefeller Nobel Prizes by Joseph Luna in June 2016.

Günter Blobel (May 21, 1936 – February 18, 2018)

Let’s start with a fantastical scene: picture a band of Neolithic humans in a hot air balloon overlooking modern New York City. What would they see and experience? Lacking a vocabulary and a mental model of twenty-first century life, our ancient friends would be awestruck at seeing miniscule specks and strangely ordered structures, lines and squares, in green and gray. Perhaps the occasional yellow rectangle from which specks would enter and exit would catch their attention. Or they might ponder a box with flashing lights, speeding its way across a grid. It’s near impossible to imagine being in their shoes, but it’s easy to envision the excitement as they try to describe and make sense of what they saw.

This totally novel experience wasn’t far off from what early cell biologists encountered, as they used the electron microscope (EM) as a sort of hot-air balloon to discover the cities inside cells. By the mid-1960s, they had plotted the geography of all sorts of cellular worlds, had given names to energy-making blobs and recycling vesicles, and with the help of radioactive amino acid labeling, had a basic sense of where proteins were made and where they ended up. But big questions remained such as how did a protein know where it needed to go? For a discipline built on EM observations from high above, this was a challenging question to answer, but it captivated a young German post-doc enough to dream as if he landed his hot air balloon and walked among molecules, where the view was much clearer.

Günter Blobel arrived in George Palade’s laboratory in 1967, shortly after completing his PhD at the University of Wisconsin at Madison. He joined a dynamic group of researchers who had stumbled upon an odd observation concerning the protein factories of the cell, its ribosomes: proteins destined to remain inside the cell were often made from a pool of freely cytoplasmic ribosomes, whereas proteins meant to be exported from the cell quickly associated with ribosomes attached to the endoplasmic reticulum (ER). How a new protein made this decision to stay in the cytoplasm or go to the ER was a mystery.

Within a few years, and overwhelmingly without much evidence, Blobel and a colleague (and Rockefeller University alum) named David Sabatini formulated what became known as “the signal hypothesis” that might explain how proteins got sorted to their proper locations. It represented a truly imaginative and startlingly precise leap, as if one could envision a five digit postal code and a stamp authentication system simply by watching mail trucks from space. Blobel and Sabatini proposed that ER destined proteins contained a special stretch of amino acids that acted like a signal that became apparent the moment the protein was being made at a ribosome. This signal sequence, located at the head of a protein, would be recognized by a factor (or factors) that would, in turn guide the synthesizing ribosome to the ER, where the protein in question could finish being born as it translocated across the ER membrane. Once properly sorted into the ER, the signal sequence was no longer needed and could be removed by an enzyme, even while the protein was still being made. Once finished, the protein could then go and do its job.

For many, this all sounded needlessly baroque. One attractive alternative was to consider different types of ribosomes, where each type was responsible for ferrying a nascent protein to a particular location. Another idea postulated that the mRNAs encoding proteins somehow got to the correct place before undergoing translation from any nearby ribosome. The signal hypothesis was one of many possible models, and a far-fetched one at that. But it made very precise predictions that could be tested, the first of which was the existence of a transient signal sequence.

Myeloma cells provided the first toe-hold for testing the signal hypotheses, since they secreted lots of IgG antibody light chains that could be readily detected. Using cell-free translation systems, based on these cells, other laboratories had observed slightly heftier IgG molecules than those secreted from intact cells, suggesting that a larger precursor was made and pruned to a final, smaller form. Yet, worries of an in vitro artifact abound. Blobel first repeated this experiment, and once confirmed, tinkered with his cell free system to uncover the order of events. Using detergent, he separated ribosomes from bits of ER (called microsomes) and added a drug that blocked new IgG production. He then let the ribosomes that had already started making an IgG to finish, keeping track of what they produced and when. Early in the experiment, only the smaller form emerged, which made sense if these ribosomes had already been at the ER and were nearly finished making IgG when Blobel had isolated them. But later in the experiment, a mixture of larger and smaller forms showed up: ribosomes that had just started making IgG indeed made a larger version. But lacking sufficient ER targeting, the signal sequence wasn’t pruned efficiently. Blobel had glimpsed a totally new feature in the early lives of proteins.

This was just the start. Over the ensuing years, Blobel and his team devised ways of recapitulating numerous aspects of protein targeting in the cell, from isolating the complex that ferried a signal sequence bearing protein to the ER (the aptly named “signal recognition particle”) to later confirming and characterizing the protein channel at the ER (the translocon) that nascent proteins traversed for proper processing. In part because of Blobel’s efforts, the hot air balloon view gave way to detailed explorations from the ground. A dream, as all good hypotheses are, turned out to be true.

Picture: Jason Banfelder, Director of the RU High Performance Computing Systems, talking about the most commonly used computing tools at the inaugural meeting of the SciComp group.

On April 12, Scientific Computing Users Group (SciComp) of The Rockefeller University’s (RU) held its inaugural meeting in CRC 406. The founders of the group, Jason Banfelder, Director of the RU High Performance Computing Systems (HPC), and first year graduate student Jazz Weisman, led the meeting. I caught up with Jazz Weisman about this new group on our campus.

NS: How did you and Jason come up with the idea to start the SciComp group?

I attended Jason’s Quantitative Understanding in Biology course at Cornell University and wanted to learn more. When I asked him about opportunities he said that starting a group is always a good, as well as a feasible idea. In fact, he had thought about starting something for a while as well. I actually recommend Jason’s lecture, or a similar intro level data analysis class, to everybody. A lot is already going on in that area, and we tried to create something in this pool. The future is definitely more computed, and we have to start somewhere.

NS: What do you think is the biggest plus of the SciComp group?

Painful and repetitive work should be reduced as much as possible. So many things can be done a lot easier with the help of computing, which will make repetitive tasks in science a lot less painful. But there are a lot of side benefits to our group. People get to know Jason as a representative of the IT department, which will make communication between the scientists in the lab and IT easier. People tend to be a bit shy about their computer skills, and we hope to make the IT department more accessible. Finally, we want to get interested people together. Labs can sometimes be a bit insulated; however, their computational interests would be similar.

NS: Researchers (myself included) can sometimes be a bit scared of using new programs, even though we use computer programs daily. Why do you think that is?

I think most are afraid of messing up their data. We also don’t want the design of our results to change, since we have long chains of experiments, sometimes generated over years, and a change in the output can sometimes make it hard to represent data neatly. But, as I said, most of our experiments come in long chains. Programming languages, such as R, Python or MATLAB, can simplify such tasks, and are actually a lot faster and easier to use than, for example, Microsoft Excel. Most importantly however, they make things repeatable, which is always better. If we use code to perform a string of tasks, this code can be given to a new student for example, and everybody can be sure the desired analysis was executed exactly the same way as usual. The student, on the other hand, can also study the string of code in peace and quiet, which will make understanding of the method easier for the new student as well.

NS: What can people expect from those meetings? Are there exercises that you do on computers together, or is it more of a discussion round?

Our group meetings usually start with a short talk of approximately 15-25 minutes on a chosen topic. For example, in our second meeting on May 18, we chose to talk about the data visualization tool ggplot2. After the presentation, we hope to get an open discussion going where everybody can ask questions. You can bring your laptop because it can help showing others the actual problem you are experiencing. It is not necessary that you attend the whole meeting; you can also just come for one part of it. We want our meeting to be an open thing. Also, we understand that everybody is busy and that you might have limited time for stuff.

NS: Who can attend the SciComp meetings? What skill level is expected from participants?

Absolutely everybody can attend our meetings and no previous experience is required. If you want to learn more on the discussed topic, please come. We expect nothing and are simply happy you are interested. If we talk about an R-based tool like ggplot2, for example, it will all make a bit more sense to you if you know some of the programming language R already. But it is not expected at all. We want the group to be widely accessible. Everybody who wants to should come!

NS: What do you expect from the participants (ask questions, prepare, etc.)?

People shouldn’t be afraid to get a discussion going. We are happy to answer the most basic questions! This is exactly why we thought the group environment would be nice, just to make everything more laid-back and relaxed. Ultimately we hope to also see group members helping each other out, with me or Jason only assisting when needed.

NS: What topics will be discussed in the meetings?

People can actually vote on which topic will be discussed. In this Google group, people should add their requested topics. If you and your colleagues want to learn about a specific program your lab is using, you should individually log onto the Google group and vote, so we can see how big the demand is. With this approach, reruns of hot topics are also possible if needed; just reenter the topic into the Google group. We hope to soon talk about DNA or RNA sequencing, which I definitely think is the topic most people are interested in at the moment. In addition, we will use the Google group for general updates as well as a place for people to ask questions.

NS: In your inaugural meeting, you talked about the most successful tools currently available to get a feel for the needs and interests of the attendees. In the last meeting you discussed the R plotting tool ggplot2, which makes all kinds of beautiful plots and graphs. When will the next SciComp meeting take place and what topic will be discussed?

We’ve decided to have the next meeting on August 3 in CRC 506 from 5:30 – 6:30. We will discuss Dynamic documents in R, presented by Thomas Carroll, head of the new bioinformatics resource center​. Finally, if anyone is interested in becoming a co-organizer they should contact me via email at jweisman@rockefeller.edu. I think that one or two more people to plan and put the word out could be a good thing for the SciComp group.

Jason Banfelder, Director of the RU High Performance Computing Systems, talking about the most commonly used computing tools at the inaugural meeting of the SciComp group.

First, there were horse-drawn wagons. Then, during the industrial revolution, the steam engine took over and ultimately helped to win the West. But all of these achievements seem to pale in comparison to what the venerable Metropolitan Transport Authority, MTA for short, has unveiled on New Year’s Day: The new Q train extension, which for the first time in thousands, nay, millions of years, connects the rural more eastern side of a part of the Upper East Side to downtown Manhattan.

But jokes aside, it might seem weird to outsiders, the very intimate relationship we New Yorkers have with our subway system. A big part of the reason being that most of us don’t have a car and heavily rely on the old underground railway system to get to work, to this new must-go restaurant in Bushwick, or that special Starbucks with just the right amount of distraction to musefully work on our screenplays. Of course, this dependence has its downsides, most dramatically felt when trains aren’t running properly, which, let’s face it, is all the time. In fact, the MTA has an actual smartphone app solely dedicated to informing us about service changes during the weekend (called “The Weekender”)! But wherever you are on the MTA love/hate spectrum (please don’t get me started on the F train!), you have to acknowledge the sheer size of the operation: 6407 subway cars distributed among 35 lines running on a total length of 380 km (236 mi), and transporting over 5 million people on a typical weekday (over 1.7 billion (with a B!) per year). Which by the way happens 24 hours a day, 7 days a week. To the MTA’s credit, they are, at least for the most part, keeping this beast running. In addition, they are even trying to further expand the network and this is where the new Second Avenue line comes in.

This feat has been a long time coming. Originally proposed almost a century ago, the actual construction never got off the ground mainly due to the Great Depression kicking in. However, the plans were brought back on the table after the demolition of the Second and Third Avenue elevated tracks (1942-55) left the Lexington Avenue line (serviced by the 4,5 and 6 trains) as the only option for commuters on the Upper East Side. And everyone living and/or working there today knows that, particularly during the week, those trains are bursting at the seams. Construction of the first tunnels began in 1972, but had to be halted again in 1975 due to New York City’s fiscal issues at the time. Nonetheless, the city’s development never stopped, leading to an ever increasing number of subway commuters, further exacerbating the situation on the Lexington Avenue lines. Finally, in 2007, after thirteen years of (re-)planning (and, of course, many quarrels about costs and the actual route), the second attempt to build the Second Avenue Subway was undertaken. According to the MTA’s vision, the new line will be built in four construction phases that will take… actually, no one knows how long it will take; The MTA isn’t even trying to give an estimate. What we do know is that the fully completed line is supposed to run along Manhattan’s east side from the financial district (Hanover Square) all the way up to East Harlem (East 125th Street). And the other thing we know is that, as of last month, the first construction phase extending the Q line to the Upper East Side has been completed, baffling the natural skeptic/cynic that is alive and well in every New Yorker’s soul.

The daredevil that I am, I have already logged a sizable number of rides on the new Q, which connects the Lexington Avenue-63rd Street station with three brand new stations on the Upper East Side’s Second Avenue at 72nd, 86th and 96th Streets. So what’s the verdict? Is the new Q faster, better, stronger? For everyone at the Tri-Institutions and around, the answer is a resounding… it depends. It depends on where you live but even more, whether you do a lot of dining, shopping, etc. on the Upper East Side. Personally, I do like the new Subway. I’m saying this, not because the new stations are really gorgeous (which they are!), and also not because I get to work significantly faster (and when it’s raining, probably drier as the closest entry to the 72nd Street station is already on 2nd Avenue/69th Street). I’m saying this, because I do enjoy certain places on the Upper East Side, which were inconvenient to get to from work, because walking to Lex just to ride the subway for one stop and then walk back to 2nd Avenue doesn’t really make sense. But also areas that are further uptown (and would make a little more sense to take the 6 train) are now easier to reach, like the one around 86th Street, where you might find me shopping at Fairway (and by Fairway, I of course mean Shake Shack) or going to the East 86th Street Cinema (again, Shake Shack). So overall, even if the new subway might not revolutionize your way of living, it at least opens up some more possibilities to travel to this mystical northern territory. And whether or not you’ve already acquainted yourself with the Upper East Side yet, now is the perfect time to get to know some great new places around Second Ave, and I’m sure that soon we will see each other buying bread at Orwasher’s, slurping ramen at Mei Jin or inhaling a burger at… well, you know where.

This year’s Rockefeller Postdoctoral Association (PDA) Retreat was held from September 21 to 22 at the Interlaken Inn in Lakeville, CT. The Interlaken Inn is a charming country resort with great facilities and over 130 Rockefeller postdocs came to enjoy this getaway. Many supported the event with presentations, ranging in scope from social evolution in ants, aphids and their interacting microbiomes, through to visual signaling in Drosophila.

The PDA further organized a panel discussion focusing on non-academic careers, which was one of the highlights of the retreat. Candid responses to heartfelt questions were given by George Yancopoulos, the President and CSO of Regeneron Pharmaceuticals, Inc., who also gave the retreat’s keynote address, Nadim Shohdy (Director, Office of Therapeutics Alliances NYU Langone), David Pompliano (co-founder & CSO, Lodo Therapeutics), Imran Babar (Private Equity / Venture Capital, OrbiMed Advisors & VP of Scientific Affairs, Rare Genomics Institute), Yaihara Fortis-Santiago (Director of Science Alliance, the New York Academy of Sciences), as well as two Rockefeller insiders, namely our new President Richard Lifton and our Career and Professional Development Director, Andrea Morris. The speakers depicted the advantages of dropping into a non-academic field and attempted to boost our self-confidence for trying out such alternative career routes. In some cases maybe even out of a personal recruitment interest?

A bonfire by the scenic Lake Wononskopomuc brought the first day come to an unforgettable end. S’more roasting gave the postdocs energy after burning themselves out on the dance floor. After another round of talks in the morning, playing tennis, sunbathing by the heated pool, kayaking and swimming in the lake in the afternoon, everybody reluctantly made their way back to New York City on Thursday night.

Imagine that you are just out of graduate school and about to embark on a biomedical science post doc in a world-renowned research institute. You have your Ph.D., you feel self-assured, confident, and certain of your path in life. You are excited about this next step and don’t care how demanding it could be compared with your Ph.D. But in a moment of doubt, you pause to consider what it might mean to be an academic scientist: what have you gotten yourself into? Many thoughts and unanswered questions about your future career will run through your mind. “Will I be strong enough to withstand the pressure? Will the impact of my research be high enough? Will I publish in good journals fast enough?” Faster, Higher, Stronger… And you dive in, that moment when the Olympic motto expresses the career aspirations of a well-driven scientist.

Most would agree if I said that many of us dreamt from the start of achieving greatness in our careers, and embraced this motto just as if we were getting ready to run the Olympic marathon. Science can be compared to endurance running, where the stamina of researchers is tested and culminates with the ultimate goal, a groundbreaking, game changing publication that will help them secure a top academic position or that sought-after industry job.

Our guest, Dr. Sohail Tavazoie, is a great example of a top player achieving greatness in this scientific field, breaking records every step of the way. He received his Bachelor of Arts in Molecular and Cell Biology at the University of California, Berkley. He also has an M.D. from Harvard Medical School and a Ph.D. in Neuroscience from Harvard University. Tavazoie then spent time as an oncology fellow at Memorial Sloan Kettering Cancer Center and conducted postdoctoral research in Joan Massague’s lab. During this time, he changed fields from developmental to cancer biology where he began to focus on the control of breast cancer by microRNAs. This was a fortuitous transition, because shortly after, he crossed Manhattan’s York Avenue to start his very own lab at The Rockefeller University. Dr. Tavazoie’s lab has been trying to understand different cellular situations where cancer cells are being regulated by small RNAs. Every project in his lab poses a new challenge. As a result of his continued success, Dr. Tavazoie has received much recognition and many honors: ASCO Young Investigator Award, Emerald He Foundation Young Investigator Award, and the Pershing Square Sohn Prize among others.

I met Dr. Tavazoie at his office, and what was supposed to be a ten minute chat turned into an afternoon of riveting conversation. Whether it was because I also work in microRNAs and tumor progression, or perhaps it was because I enjoyed his fascinating responses to our questionnaire, or maybe even, because he mentioned a fondness for Madrid, my hometown, I sat there enthused by his passion for science and his wonderful achievements in such a short career.

NS: Who, or what, inspired you to enter your field of achievement?

ST: It happened during a science summer program when I was in high school. John Roth, who was a bacterial geneticist, exposed me to science for the first time and that was what hooked me. Later, when I was in college, I got a job in a lab washing the glassware to pay for my college tuition. While I was there, I made a deal with the scientist from the lab I was in, half the time I would wash the glasses and half the time he would let me do research. That was great to do experimental science again during college, but looking back I would really say that it was my high school experience, when I was 16 and worked with John, who made bacterial genetics super exciting, that is what definitely got me hooked on science and I could never go back from that.

NS: Explain your work to a five-year-old.

ST: When people get cancer sometimes the cancer can spread to other organs in the body and that is called metastasis. When it is spread to other places, the cancer cells can grow in those organs destroying them and patients can die. The biological question is how is it that some of those cells that belong at the primary tumor site can colonize other tissues. Experiments have shown that out of every ten thousand cancer cells in circulation, roughly one is able to ultimately form a metastatic colony. We are trying to understand how this single cell is able to do that and how it can shift its gene expression program to be successful in colonizing other tissues. We have seen how those cells are able to change the lifespan of their RNAs. By increasing the stability of those RNAs of genes that promote growth and metastasis, and suppressing the genes that negatively impact on them, they are able to form the malignant colonies. We are interested in better understanding the process by which those cells are able to shift the level of those genes’ RNAs and we have seen that this can be achieved post-transcriptionally by diverse small RNA types. We have observed that similar gene regulatory mechanisms also operate in normal cells to control the levels of gene expression normally. Probably not for a five year old kid though.

NS: If you could sum up the most important characteristics of a scientist in three words, what would they be?

ST: A scientist should be passionate, rigorous and hard working.

NS: How does creativity play a role in science?

ST: I think that creativity plays two roles. The first is that creativity is important in the initial inception of what you are going to study and what you want to pursue, the biological question that you are interested in. Creativity also comes into play by enabling you to utilize new technologies and creating new approaches in order to specifically address your … questions.

NS: Scientists are not only focused on science. They are usually passionate people devoted to other extra-curricular activities. Do you have any other passions besides science?

ST: I used to. Right now my free time goes to my children…I used to play sports, I love[d] to run track and field, played a lot of basketball, skiing, rock climbing. Once you have children, things change and kids become your hobby. Right now, the kids drain all my free time, but every now and then, my wife and I take some time for ourselves and enjoy this beautiful city.

NS: What would you be if you weren’t a scientist?

ST: … I trained as a physician, I am a medical oncologist and I am still seeing patients at MSKCC. If I wasn´t a scientist I think I would do that full time. In my opinion, medicine has become … more and more scientific, and medicine and science have a lot in common. We need more effective cancer therapies for patients and that motivates me to continue to understand how cancer behaves. I think being a scientist is the best job one can … have, and being a physician would be the second best job.

NS: Did you have any big rejections in your life?

ST: Absolutely. As you grow up, there are things you aspire for that you don’t achieve. In track and field, there was always someone faster than me. During high school and college there were rejections. When I applied for grants there have been many rejections. There have been rejections also in paper submissions. I think rejections are key, because you want to know that not everything is easy and you need to get a sense that you can’t have everything you want. That you have to work hard for what you want. Life is many times not fair and you can work very hard and not get what you fought for. Rejection builds character and forces you to elevate your game. In science in particular, you need thick skin and can’t let frustration take over.

NS: Who, of all the historic or current personalities, would you most want to meet and why?

ST: That’s a good question. I would like to meet Oswald Avery of Avery-MacLeod-McCarty fame. He was a professor here … and they were the first [group] to show that DNA is constitutes the molecular basis of heredity. It is sad that he never got full recognition for that. From what you can read about him he seems to have been an outstanding scientist, an incredible thinker, and someone with tremendous integrity. I´d love to meet him and have a better understanding of his persona and how he could inspire the younger scientist[s] around him who transmitted his own approach.

NS: What’s your idea of a perfect holiday/vacation?

ST: I would say … in a Mediterranean beach resort with great food, enjoying time with my family and having time to read books about history and science that I am really into.

NS: Do you have any advice for young researchers?

ST: Take your time to find the question you are interested in. Talk to senior scientists who could be your role models and inspire you. Try to find out how they take their path in science. Try to push yourself into areas that are understudied. Find a good environment that allows you to grow and express yourself. One doesn’t have to stay in academia, if you find it in biotech [biotechnology companies], just go for it. There’s great science done in biotech, as it is in academia. Communication is a big part of science, so I would tell them to practice their teaching skills, it helps your lectures and your ability to write, and the better you communicate, the better scientist you will be.

Of the 37.2 trillion cells in the human body (excluding microbes), there are about 100 billion, or about 0.2%, that are a breed apart. These supercharged cells are indeed just that, charged to carry electrical signals to communicate with one another. They are organized into a dense and almost unfathomably complex network that uses gobs of energy to act as a command center for everything humanly imaginable. These cells control your breathing, your ability to see, and initiate every movement you make. They are responsible for every idea you’ve ever had, every feeling you’ve ever felt, and every memory you’ve ever recalled.

I’m writing of course, of the neuron, the basic cellular unit of the brain. Because of their almost mystical properties, generations of scientists have dedicated entire careers toward understanding how neurons work. Nowadays, we call such devotees neuroscientists, but this wasn’t always so. When our next future Stockholm visitor got started, the basic truths outlined above were known about neurons. But they remained a black box: so little was understood about neuronal insides that neuroscience wasn’t yet a distinct field in the mid-1950s and early 1960s. For a newly minted PhD named Paul Greengard, this soon became an inspiring frontier.

Trained as a neurophysiologist at Johns Hopkins, Greengard was thoroughly grounded in the electrophysiological school that viewed neurons essentially as living electric cables. In other words, everything important about the brain could be explained through an electrical understanding of how neurons communicated with each other at short timescales. By understanding the biophysics of a firing neuron, it was believed that a largely complete understanding of the brain was possible. And yet, neurons weren’t inert conduits: to the biochemists, they contained scores of unique enzymes and molecules that at first glance had little to do with the rapid electrical wizardry for which neurons were famous. As living entities, they were likely much more complicated than electrophysiologists believed. Not surprisingly in this situation, neither side took the other seriously.

One feature of neurons as cells caught and kept Greengard’s attention: neurotransmitters. In the normal rapid communication between two neurons, an excited neuron releases specific molecules to stimulate a neighboring neuron, a bit like passing a message with a direct handshake. This fast synaptic transmission as it was called, was carried out in milliseconds. But there were dozens of other neurotransmitters that appeared to act much slower, on the scale of dozens of milliseconds to seconds, sometimes minutes. This slow synaptic transmission presented a bit of a puzzle. No one knew how it worked, or largely what it was for.

Greengard’s great insight was to pay attention to the biochemists. Starting from the premise that a neurotransmitter was a small chemical messenger between two cells, Greengard was encouraged by work with hormones, as a similar form of cellular communication. What made hormones remarkable was their ability to act at long distances, a hormone made in the pancreas could travel through the bloodstream and instruct a distant liver or muscle cell. Greengard hypothesized that neurons might be using similar principles, without the long distances. It was a bit like saying that in a world where quick handshakes were king, neurons were also using phones, fax and email to talk to one another.

The early neuroscience community was skeptical that any long distance communication was needed in a fast synaptic transmission world, but Greengard had a decisive edge. He knew from the biochemists that when a hormone reached its target cell, a specific enzyme called an adenyl cyclase was activated to make a molecule called cyclic adenosine monophosphate (cAMP), and both the enzyme and cAMP could be reliably measured. Then at Yale, Greengard and his first postdocs tested to see if such an enzyme existed in the brain that could make cAMP. To their surprise, they found that the adenyl cyclase levels were not only higher in the brain compared to other tissues, but that a slow acting neurotransmitter called dopamine was needed to activate the enzyme. This was a first peek inside neuronal machinery, and it confirmed that the signaling that went on inside of neurons was consistent with other cell types. Suddenly an entirely different layer of communication and regulation of neurons was on the table.

Starting with a dopamine-sensitive adenyl cyclase, over the next three decades (and persisting to this day), Greengard and his laboratory, in no small part, created much of molecular and cellular neuroscience by charting the order of intracellular events triggered by a neuron engaging a neurotransmitter. First with biochemistry and neurophysiology, and later with molecular biology and mouse genetics, the Greengard lab showed that these slower signaling pathways didn’t replace the fast communication between neurons, but rather they modulated them: they acted like the knobs and dial settings that enabled the brain to run smoothly. These discoveries had enormous implications for a variety of neurological and psychiatric diseases associated with abnormal dopamine signaling, from Parkinson’s disease, schizophrenia, ADHD, and drug abuse. Molecular explanations of how drugs worked on the brain were now possible, not to mention inspiring whole new avenues of therapeutic intervention.

One might expect that as the neuron gave up many of its secrets, fewer would have been drawn to it. On the contrary; because of the efforts in Greengard’s lab, the neuronal muse continues to inspire current and future generations of scientists. Mystery yields to awe.

July 23, 2012—that’s the oldest record that I can find in the running app on my phone. Distance: just under two miles. Back then, I could probably never have imagined that I would be running the 26.2 miles of the New York City Marathon three years later.

Running was never my strongest suit. In college, I only ran a few laps around where I lived because my primary care physician told me to. Usually after I hit two miles, I was quite exhausted. Running was nothing but a chore and losing motivation was the obvious consequence. So I had become accustomed to running two miles at a time and never thought about running more. One day, I noticed that somehow I managed to complete my chore run without losing my breath. “Oh, maybe I can run longer,” I thought.

ROBYN SPECTOR/ROBYN SPECTOR MEDIA

From that day, three-mile runs became my routine. When I moved to New York after college, I started to run in Central Park. It was a rather eye-opening experience. Since then, running in Central Park has become my addiction. Things like the sunrises over the reservoir, the summer fireflies in the twilight, and countless other fellow runners have kept my motivation high. It did not take me long to feel that I wanted to do something more; so, that year, I signed up for a three-mile race for the first time.

Fast forward a year. I now had a bunch of 5-10K races and several half-marathons under my belt. I won a spot in the New York City Marathon, via the lottery. Entering the New York City Marathon was partially due to my sheer spontaneity and recklessness. Actually, I was not confident at all that I could run the entire 26.2 miles, but I thought why not give it a try. Perhaps I wanted to prove something to myself that I could. Because from what I heard, running through all the five boroughs of New York City was supposed to be an unforgettable experience; and it really was.

On marathon day, I left my apartment on the Upper East Side at 5:30AM, wrapped up in my friends’ warmest words of encouragement. Nobody was on the street, but from the moment I stepped inside the subway station, spotting my fellow marathoners was not too difficult. A guy who probably was coming back from his Halloween party asked me if all the express trains were running local. I said yes. Then he asked me if I were running a marathon. I said yes again with a nervous nod.

“I could never do that! Good luck!” he said. “Thank you, Mr. Indiana Jones,” I thought.

I was supposed to take the 6:15AM Staten Island Ferry. Obviously, the terminal was packed with hundreds of runners and I had to wait to take the next ferry. I had taken the ferry a few times before, so I decided to skip being a tourist and sat in the corner to catch up on some sleep.

“Hey, are there any outlets on your side? Need to charge my iPod.” the guy next to me asked. He was probably around my age. I couldn’t find any outlets, but then we started chatting. “I’m Garrett, by the way” he said.

Garrett and I had different start corrals but it was pretty comforting and relieving to have company. It was quite a wait from the time I entered the designated corral to the starting line, but the time eventually came.

“So it’s finally starting,” I thought.

While I walked to the starting line, I suddenly got somewhat nervous and overwhelmed by the number of runners, but my nerves quickly diffused as I discovered that I was filled with anticipation for what I would discover and experience for the next three hours.

Yonkers, New York. But most people say Rockefeller University, ha! “1 tostado Plaza!”

Which is your favorite neighborhood?

I’ve lived in Harlem, three different parts of Queens, now I am in Yonkers. But I have to say Harlem. I grew up with some great people. I love the Rucker games. And even though they had gangs and violence, my mother raised me right so those things never influence me. I like to say “it don’t make no difference”.

What do you think is the most overrated thing in the city? And underrated?

Overrated? I think cleaning the bus stops, I think it’s a waste of water. Underrated? Water! People waste a lot of it.

What do you miss most when you are out of town?

If I EVER leave, Home sweet home…

If you could change one thing about NYC, what would that be?

People who cross the street with headphones in their ears, not paying attention. Especially when I am driving.

What is your favorite weekend activity in NYC?

I love my DVDs. Karate movies. The best martial arts action-packed film was Expendables 3. It had everybody in it. Jean-Claude Van Damme, Chuck Norris, Sylvester Stallone. Man, I would have to lend you the DVD. Anything with action gets my attention.

Has anything (negative or positive) changed about you while living here as a New Yorker?

My Sensei, Jose Santos. Because of him I am still teaching exercise classes at Rockefeller. He taught me discipline, and the right way of life. He’s the reason I am the way I am today. Negative? NOTHING! People always see me smiling through the hallways all day long and ask how I do it? How do I always stay happy and smiling? I say “It’s healthy for you. You should try it.”

During the summer months, I try to use the campus walkways to go between buildings, rather than the tunnels. Recently I was walking along the East Walkway, behind the Student’s Residence, near Bronk. I stopped when I noticed a sign I hadn’t seen before: “The Lila J. Magie Garden, In recognition of Lila’s outstanding service to The Rockefeller University from 1950 to 1991.” I wondered, who was Lila J. Magie and why did the University name a garden after her?

Photo: Lila Magie with David Rockefeller, by Leif Carlsson

It turns out that she was a well-liked, long-term employee who left her estate to the University when she died on December 23, 2012. She was a native New Yorker, born in 1927, who went to Washington Irving High School. Magie received a degree from the Purdue University’s School of General Engineering in Liberal Sciences and started at Rockefeller in 1950. Her first position was as a stenographer in the business office. She then moved up to secretary in that office, then moved to personnel. She became responsible for staffing from 1954 until 1987, when she was promoted to the Director of Faculty Administration and Secretary to the Board of Trustees. Magie retired in 1991 and moved from Bronxville, NY to Rockland, ME, where she continued her gardening hobby.

While most of her career was in Human Resources (HR), her positions allowed her to interact with many different people on campus, from academic personnel to board members. She was known as the “go to” person around campus if someone needed to know something; the common phrase was “Go ask Lila.” Magie once took care of a school of pike for Dr. Herbert Gasser while he was away. HR was a good fit, since she had a reputation of being well liked by everyone. As Isiah Curry remembers her admiringly, “She was Human Resources.”

There was a dedication ceremony for the garden this past June, led by Marnie Imhoff, Senior Vice President of Development. During the ceremony, she talked about how when Magie retired, the University community put together a scrapbook of messages to her. There are entries of numerous people who knew and worked with her, including David Rockefeller, Brooke Astor, Christian de Duve, and Joshua Lederberg. The entry from Dr. Lederberg reads “Dear Lila – The stories we could swap… but don’t dare put to paper…”

When The Rockefeller University learned that Magie had left her entire estate to it, it was decided to dedicate a garden to her, since she was known as an ardent gardener. Rockefeller’s horticultural consultant, Lulu Leibel, chose from a list of flowering plants with Magie in mind, which also do well in the shade. There is a pink flowering dogwood tree in the garden. There are several flowering shrubs, including two different kinds of hydrangea, a holly bush and a lilac bush. Other flowers were planted there too, pink Astilbe, a pink coneflower, a heritage rose, and some Salvia. There are also several ferns and ornamental grasses in Magie’s garden.

This garden is evidence of what a great community culture we have here at Rockefeller. There are many long-term employees, for whom the University is like a second home, this author included. Also, check out Amelia Kahaney’s article about Magie in the next issue of Benchmarks to learn more about this venerable member of our campus.

Living in New York, most of us often find ourselves trapped inside concrete jungles, busy and occupied all the time. Sunshine and the view in the distance from our windows are often blocked bluntly by another building. On the subways, we look down, napping or playing with cell phones, avoiding eye contact. We talk fast, walk fast, eat fast-food and couldn’t go through a day without our caffeine shot. Slowly, we start to forget the world outside, a world that is organic and original.

One day, I stopped by the Employee Art Exhibition on my way to get lunch in the Weiss lobby. A series of acrylic paintings caught my attention. There was a vivid giant lion head about to leap out of the paper with his fur standing on end and both eyes gazing ahead; a baboon mother watching her baby playing in the grass; an elephant enjoying his shadow in the river with his ears wide open and a majestic giraffe sticking her head above and over tree leaves against the blue sky. I was very impressed by the painting’s details, the strokes, the color, the light and shadow, and the background. More so, I could feel there were feelings and stories behind these paintings and I was compelled to find out more about them. On the 13th floor of Weiss, I met up with the artist, Dr. Bruce McEwen, a distinguished neuroendocrinologist, in his office.

Acquired somewhat from his heritage, Dr. McEwen has enjoyed drawing since his childhood. He started painting about 15 years ago, starting with water colors. In recent years, he fell in love with acrylic painting. His paintings in the exhibition were inspired by his wife’s wonderful photography, which was also on exhibit. Both Bruce and his wife, Dr. Karen Bulloch, are talented artists who make a variety of art pieces in their leisure. In the summer of 2014, they went on safari in southern Africa with a group of scholars. Being a travel lover, I immediately became fascinated with their safari experience. It was the couple’s first trip to Africa and a trip like never before. They had never been in such close proximity to hippos, rhinos, lions, giraffes, and even at the mercy of a charging elephant. The reality of seeing these animals, Dr. McEwen said, was surreal, completely different from visiting a zoo. It felt like Jurassic Park. In the safari park, the couple was covered in dust every day. Tourists were tucked in the back of open trucks covered only with metal fences. Wild animals could care less about human presence, especially when there are prey in sight. It seems quite certain that they assume the leading roles, and tourists are just extras. Locals have to learn to co-exist with these wild animals, protecting themselves and sharing resources. It is a real eco-system, a world where hyenas tear a giraffe apart and share dinner among themselves.

Unfortunately, these animals’ real enemies are not themselves, but humans. To date, there are still many greedy, selfish slaughterers out there killing elephants for bloody profit. Bruce told me that the safari security personnel were equipped with guns not to protect visitors per se, but to defend wild animals against any illegal hunting.

What struck the couple most and brought them to deep reflection and awareness is the extreme gap between rich and poor and the importance of the middle class. They visited several village schools made of adobe and wouldn’t soon forget the expression of excitement on the faces of those school kids when given a soccer ball. “They were all very smart,” Dr. McEwen said, “We don’t realize how much we have.” As a matter of fact, Karen, a fantastic photographer, captured and documented some precious moments of their school visit on film, which were also on view as part of the exhibit in Weiss lobby. The couple has made and kept a connection with local schools there and they sincerely hope their continuous outreach arrives soundly in the hands of those in need in the future.

My conversation with Dr. McEwen had to end, but it lit up my dream of Africa. Although seemingly a far-reach right now, one day it can happen, and it will happen. Once deeply enchanted by the classic film Out of Africa, I can’t wait to step into Africa, to soul-search, to feel, to perceive and to understand simple happiness in life.

Social psychologist Jonathan Haidt, in his brilliantly written book TheHappiness Hypothesis, summarized three ways that people generally view their work: a job, a career, or a calling. A job is what people do to earn money and to support their families. A career is what people do to achieve higher goals, such as advancement and prestige. A calling, on the other hand, is for those who find their work so intrinsically engaging and fulfilling that they do it for the sheer love of it. These people usually would continue to work even without pay, if they suddenly became very wealthy. They would have found their life’s vocation.

How do we find ours? In many ways, this is an age-old question. Two and a half millennia ago, Confucius advised, “Choose a job you love, and you will never have to work a day in your life.” Nowadays in industrialized western society, where individual autonomy and achievement are farmers among the highest priorities, this question seems even more urgent. As Apple entrepreneur Steve Jobs, remembered as much for his passion as his success, once said, “You have to be burning with an idea, or a problem, or a wrong that you want to right. If you’re not passionate enough from the start, you’ll never stick it out.” This type of sentiment has always created mixed feelings in me. I am deeply moved and inspired, but at the same time confused and even frightened, as one question burned in my mind: what is my burning idea and would it be strong enough to motivate me to the end? For a long time, I thought my passion was out there, like some great truth, waiting to be found.

Now in its 56th year, The Peggy Rockefeller Concert Series is decidedly unknown to much of the campus community. But those familiar with the program know that some of the most accomplished musicians in the world played Caspary Auditorium as a live rehearsal for Carnegie Hall.

Since its inception, the series has featured performances in a wide array of genres, from chamber music, to Renaissance revival, to operatic arias, to jazz. Three dedicated caretaker scientists with a passion for music have shepherded the program across five decades, and kept the program afloat through rising and ebbing tides of interest within the Rockefeller community. Though performances often sell out, admission sales and private donations barely cover the program’s expenses.

The concert series traces its origin to 1958, shortly after its unique venue was unveiled. Caspary Auditorium’s geodesic structure was designed by modernist architect Wallace Harrison, who also led the construction of Rockefeller Center, the U.N. Complex, Lincoln Center’s Metropolitan Opera House, and Brooklyn’s Clinton Hill Co-ops.

If there were an epicenter for a fascination with the Nobel Prize, The Rockefeller University, with 24 such awards, would be it. For its size, the university has the greatest density of Nobel prizes of any place in the world. The big-picture factors that have led to such a prestigious legacy are ones best left to historians to debate. As a graduate student, I have two much simpler questions: what was each prize for and how were the essential discoveries made?

In this series, we’ll peel back the arcane language and suspend a bit of hindsight to explore concisely the ideas and experiments that underlie each of the university’s 24 associated Nobel prizes. From the obvious “why didn’t I think of that?” to “that can’t be true” courageous nonconformity, we’ll look into the context of the problems solved and their greater importance. For if genius really is “seeing what everyone else has seen and thinking what no one else has thought,” I wonder what truths of the scientific process can be wrought by studying examples of genius close at hand. This isn’t to say that getting a call (or telegram) from Stockholm at five in the morning is the ultimate imprimatur of genius, but, as examples of what one university has accomplished over the past century, they’ll do just fine.

So let’s begin. We’ll start our journey with something so fundamental, that we rarely give it a passing thought: plumbing.

Any organism with a circulatory system, by definition, is filled with plumbing. The human body is a veritable city of blood pipes: around 60,000 miles of vessels ferry close to 5 liters of blood, all thanks to a large and reliable heart pump. These basic components of human anatomy (of existence even), work tirelessly in the background, ignored only until something goes wrong. For a surgeon over a century ago, such failures of circulation were frustrating things to encounter. Unlike the plumbing in an actual city, where a team of welders could quickly repair a ruptured water main, there was little a surgeon could do to solve the same problem in a person rapidly losing blood. Where was the surgeon’s welding torch?

Alexis Carrel, a French experimental surgeon and the first of the university’s Nobel Prize winners, answered this call by inventing many surgical techniques used to repair blood vessels. As anesthesia and aseptic practices became widely adopted in the operating room by the early 20th century, such experimental surgery became possible, and Carrel devised cleverly simple and incredibly powerful methods that unarguably helped lay the foundation for modern organ transplantation. His basic question boiled down to this: how do I join two delicate and floppy tubes end-to-end? Many before Carrel had tackled this problem, using bits of bone or metal as rigid scaffolds for crudely sewing two blood vessels together, but complications like infection, hemorrhage, and bruising were constant problems. Carrel’s solution first required an initial detour. He left the operating room entirely and learned to sew from those who knew best: French embroiderers. Apocryphally, some say Carrel had learned embroidery from his mother in his boyhood, while others write merely that he studied under the finest embroiderers in France. What mattered was that he became so good at embroidery that his stiches across sheets of paper were fine enough to be invisible on both sides. Returning to the operating room, he perfected what is now known as Carrel’s triangulation technique for joining blood vessels together. No fancy devices were needed other than silk thread, fine embroidery needles and lots of skill, though the basic premise is ingeniously simple. Three stitches are placed at equal points around the circumference of a vessel to be joined. By pulling at these stiches, the vessel opening no longer resembles a floppy circle but a rigid triangle. Holding two such triangulated vessels end-to-end, it becomes easy to sew across the seam for a blood-tight seal (see below). Since no forceps are used to hold the edges of a blood vessel, only light and delicate silk thread, all sorts of complications were greatly reduced. Varying this basic technique, end-to-end anastomosis, Carrel performed veritable miracles of medicine. He could repair vessels of virtually any visible size (as small as “matchsticks” as one observer put it) and attach them to other vessels in all manner of ways, from junctions to loops. He devised means to repair blood vessels without exposing them to infectious agents, worked out ways to viably preserve tissues outside the body, and performed some of the first successful organ and limb transplants in animals. But Carrel’s visionary work was a full half-century before its time for wider use in humans, as he lacked antibiotics to control infection and the drugs to suppress the immune system. His lab closed upon his retirement in 1939, but the dream of transplant surgery certainly did not. As his 1912 Nobel can attest, Carrel demonstrated that the surgical part of transplantation and tissue repair was both possible and practical.

Incidentally, Carrel’s lab was located on the 6th floor of Founder’s Hall, where the gym stands today. What a sight to imagine there: a surgeon hard at work in 1912, saving a dog or a patient, carefully suturing blood vessels, aiming to forestall certain death. I doubt any have sweat more than Carrel did in that space.

It’s springtime in New York, and that means the start of baseball season. There is still hope in the air for the Mets, and great expectations for the Yankees, the two New York teams.

Baseball is known as the “Great American Game,” illustrated by a commercial from about 30 years ago, which ran with the tagline “baseball, hot dogs, apple pie, and Chevrolet.” It is unclear exactly how American the game is. For many years it was a common belief that Abner Doubleday invented baseball in 1839 in Cooperstown, NY. The belief comes from the Mills commission, a 1905 report by the National League. This was the basis for the location of the Baseball Hall of Fame. In recent years it has become known that this origin is a myth. Abner Doubleday was a Civil War general, but he was a cadet at West Point in 1839, and his family had moved from Cooperstown the year before. When he died, he left many papers and letters, none of which even mentioned baseball.

The first issue of Natural Selections was published in February of 2004. In these past ten years, much has happened, on campus and off. For all that has happened, however, much has stayed the same, including the humor. This year we are republishing the best and most timeless pieces from the corresponding month in 2004.

Continuing on with our salute to the tenth anniversary of Natural Selections, here is this month’s republished comic from 2004.

What makes great art? This is a question that thinkers have been pondering ever since civilization’s infancy and I dare not attempt to answer it in less than a page. Instead, I’ll posit what makes a great artist by using, in my opinion, the classical music world’s finest champion: Ludwig van Beethoven.

Of all composers, Beethoven is probably the most well-known. Haydn wrote 104 symphonies but almost none are recognizable to the casual listener. Mozart wrote 41, but the first 20 or so are completely forgettable. Beethoven wrote only nine symphonies but at least two are so famous that even people that have never listened to a piece of classical music have likely heard them: the first movement of the Fifth Symphony (duh-duh-duh-DUH) and the last movement of the Ninth, the Ode to Joy. Beyond that, numerous other pieces of his music are easily recognizable (the Turkish March, Für Elise, and the Moonlight Sonata are examples.) But why is this? Clearly, there’s something universal about Beethoven’s musical idiom, something in the sound he produces that appeals to most humans. Therefore, universality is the first characteristic that I believe defines a truly great artist.

This month’s issue marks the tenth anniversary of Natural Selections; issue one was published in February of 2004. In these past ten years, much has happened, on-campus and off. For all that has happened, however, much has stayed the same, including the humor. This year we are republishing the best and most timeless pieces from the corresponding month in 2004.

A friend of mine, who despises classical music, once sniped to me that “the background of movies” is the only fit place for “that kind of music.” Ironically, she hit upon a truth about music, but not in the way that she initially intended. It is true that you often hear classical-esque music during movies but why is that? Perhaps instrumental music is a natural partner to visual storytelling? Classical music takes this interpretation to an abstract level: a story without words or pictures, a story entirely comprised of sounds.

No composer in history ever set about writing a piece of music “at random.” Beethoven didn’t just start scribbling notes to the Ninth Symphony (after all, there are thousands of them). He had ideas in his head that he wanted to express through music, or, in other words, he wanted to tell a story. And just like any other story, virtually every piece of classical music has a beginning, middle, and end. And there are also main characters and minor characters: primary themes and secondary themes. There’s depth and complexity to the characters, as depicted by harmonies and various types of melodic modulations. The plot itself is how the melodies transform, interweave, and reform throughout the piece, usually leading to some kind of climax and ending in some sort of resolution. Part of the fun is trying to decipher how these disparate elements combine to create the whole piece, the complete tale.

Or one can simply listen to and enjoy the music. Classical music, like every other genre of music, is simply sound that makes us feel after all. A universal theme of every culture is the creation and love of music. Classical music is the Western world’s historic contribution to this anthology. So sit back and analyze away or close your eyes and let the music tell its own story.

As of this writing, the Tri-I Concerts for December and January have not been finalized, but I present here what has been confirmed.

Went to IKEA. I thought, this is kind of sad—first day and I go to a Swedish store. But then I took the boat back to Wall Street and walked into a film shoot with the Rock and Samuel L Jackson. I was standing in front of them and thought, no, this does not feel like Sweden anymore. This is different.